Analysis of a novel repulsive axon guidance protein, Draxin

点击翻译按钮获取中文摘要

During nervous system development, correct navigation of axons to their synaptic targets is one of the essential steps to form precise and functional neural circuits. Axonal pathway selection depends on environmental secreted or membrane-anchored guidance cues. Here, we report the cloning and functional characterization of a secreted protein, which we call Draxin(Dorsal repulsive axon guidance protein).Draxin shares no sequence homology with known guidance cues, and its messenger RNA was expressed transiently during development in the dorsal part of the spinal cord and brain. Draxin induced growth cone collapse and repelled neurite outgrowth from explants of chick dorsal spinal cord and mouse cortex. Ectopically expressed Draxin inhibited growth or caused misrouting of chick spinal commissural axons in vivo. draxin deficient mice showed severe defects in axonal projection of all three commissures, the corpus callosum, hippocampal commissure and anterior commissure in the forebrain. In contrast, the habenular commissure, posterior commissure and spinal cord commissure seemed intact. Thus, Draxin is a novel chemorepulsive axon guidance molecule for commissural axons and play crucial roles, especially in the development of forebrain commissures.